Standard precautions (SP) are a fundamental set of actions, including hand hygiene and use of personal protective equipment and sharps safety devices, that every healthcare provider should perform in every contact with every patient to prevent patient healthcare associated infections (HAIs) and occupational blood-borne pathogen exposures. Despite well established, longstanding guidelines and usual training, SP are not reliably practiced, with self-reported adherence among nurses (who have the largest proportion of direct patient contact in acute care) less than 50%. HAIs are a substantial public health problem affecting approximately 2 million patients annually, resulting in 99,000 estimated deaths and occupational blood-borne pathogen exposures to 1 in 25 registered nurses. One promising mechanism that may improve SP adherence is simulation training, an emerging and effective educational approach to enhance healthcare workers' performance. This study will test a simulation intervention designed to improve provider performance of SP and prevent HAIs and occupational blood-borne pathogen exposures. The aims of this project, ?Simulation to Improve Infection Prevention and Patient Safety: The SIPPS Trial,? are to: 1) determine the effect of simulation training on nurse knowledge, observed SP adherence, and HAI and nurse blood-borne pathogen exposure rates; 2) determine whether patient safety culture modifies the effect of training on observed SP adherence and knowledge; and 3) determine maximal duration (sustainability) of the simulation intervention on clinical performance of SP adherence. Our research objectives, methodology, specification of measures, and simulation implementation plan are innovatively guided by both a conceptual framework (Human Factors Framework) and implementation model (Consolidated Framework for Implementation Research). We will conduct a 5-year group-randomized, group-interventional trial to test a clinical in-situ (i.e., taking place in a live, operational, clinical setting) simulation training intervention and include approximately 336 direct care registered nurses from a total of 12 units from two hospitals in two states. Unique survey, direct observation, focus group, and secondary data will be collected and aggregated to answer our research questions. This project will be supported by the expertise and resources from world-class academic and clinical settings committed to advancing patient safety through simulation research. Results will be disseminated in an in-situ toolkit to include a SP curriculum and video training. Hospitalized patients, including women and minorities, the elderly, inner city residents, and the chronically ill - AHRQ priority populations - serve to benefit from improved adherence to standard precautions, and health care workers will benefit from enhanced ?real world? training and support to reduce their exposure to blood-borne pathogens. Ultimately, knowledge gained from this prioritized research will inform key stakeholders of the vital role that simulation training performs in patient safety and in advancing national aims for healthcare improvement.